RT Journal Article
SR Electronic
T1 Transgenic Animals with Inducible, Targeted Gene Expression in Brain
JF Molecular Pharmacology
JO Mol Pharmacol
FD American Society for Pharmacology and Experimental Therapeutics
SP 495
OP 503
DO 10.1124/mol.54.3.495
VO 54
IS 3
A1 Chen, Jingshan
A1 Kelz, Max B.
A1 Zeng, Guoqi
A1 Sakai, Norio
A1 Steffen, Cathy
A1 Shockett, Penny E.
A1 Picciotto, Marina R.
A1 Duman, Ronald S.
A1 Nestler, Eric J.
YR 1998
UL http://molpharm.aspetjournals.org/content/54/3/495.abstract
AB Several inducible gene expression systems have been developed in vitro in recent years to overcome limitations with traditional transgenic mice. One of these, the tetracycline-regulated system, has been used successfully in vivo. Nevertheless, concerns remain about the ability of this system to direct high levels of transgene expression in vivo and to enable such expression to be turned on and off effectively. We report here the generation, using a modified tetracycline-regulated system under the control of the neuron-specific enolase promoter, of several lines of mice that direct transgene expression to specific brain regions, including the striatum, cerebellum, CA1 region of the hippocampus, or deep layers of cerebral neocortex. Transgene expression in these mice can be turned off completely with low doses of doxycycline (a tetracycline derivative) and driven to very high levels in the absence of doxycycline. We demonstrate this tissue-specific, inducible expression for three transgenes: those that encode luciferase (a reporter protein) or ΔFosB or the cAMP-response element binding protein (CREB) (two transcription factors). The various lines of transgenic mice demonstrate an inducible system that generates high levels of transgene expression in specific brain regions and represent novel and powerful tools with which to study the functioning of these (or potentially any other) genes in the brain.